Neurophysiology of Pain in Children with Cerebral Palsy

脑瘫儿童疼痛的神经生理学

• 批准号: 10313339
• 负责人: Max J Kurz
• 金额: $ 10.16万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313339
• 关键词: Neurophysiology; Pain; Children; Cerebral; Palsy

PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) is one of the most prevalent and costly pediatric neurologic conditions diagnosed in the United States. Although the brain injuries seen in these children are non-progressive, they often instigate a cascade of structural (i.e., boney malalignments, muscular contractures) and functional (i.e., co-contractions, spasticity) abnormalities within the musculoskeletal system that can become worse throughout development. These secondary changes are presumed to be primarily responsible for the chronic musculoskeletal pain that is seen in a large percentage of children with CP. However, currently there is a major lack of knowledge in this area, especially in regard to the neurophysiological mechanisms of the persistent pain, as most studies to date have focused on quantifying the prevalence of pain symptoms and not the underlying physiology. Without this critical information, the prevention, treatment and evaluation of the chronic musculoskeletal pain will not advance. Our extensive magnetoencephalographic (MEG) brain imaging program has identified that the early brain insults experienced by children with CP result in aberrant processing of the peripheral sensations by the somatosensory cortices. Recently, we have extended these results by showing that children with CP who have more abnormal somatosensory cortical oscillations following peripheral stimulation of the feet, also have higher reported pain. This relationship implies that there might be a fundamental link between the integrity of somatosensory cortical processing and the pain perceptions of children with CP. The goal of this proposal is to test our scientific premise that the disturbed somatosensory neural connections, potentially arising from maladaptive neuroplastic changes following early brain injuries, are altered in children with CP and that this leads to heightened activity in the pain perception network and chronic pain. Our approach is of “high risk”, but has the potential to be remarkably “rewarding,” as it may lead to novel insights and a paradigm shift in our understanding of pain perception in children with CP. The Specific Aims of this proposal will (1) demonstrate that the strength of somatosensory cortical oscillations following peripheral stimulation of the mechano- and nociceptors of the feet and hands will scale with a child’s perceived pain levels, and (2) determine if the strength of somatosensory cortical oscillations following peripheral stimulation are differentially altered in children with CP who have low versus high pain levels, and whether both groups differ from typically-developing (TD) children. Briefly, our study will use MEG, advanced image reconstruction methods, and time series analysis to quantify the strength of somatosensory cortical oscillations following stimulation of peripheral mechano- and nociceptors in TD children, and children who have spastic diplegic CP and different pain levels (i.e., severity). Achieving our Aims will provide substantial insight on the neural basis of chronic pain in children with CP, and may spark a paradigm shift in the mainstream treatment and assessment of musculoskeletal pain in this population.

项目概要/摘要 脑瘫（CP）是儿童中最常见、最昂贵的神经系统疾病之一。 美国。尽管这些儿童的脑损伤不是进行性的，但它们经常会引发 结构性（即骨骼排列不良、肌肉挛缩）和功能性（即共同收缩、 痉挛）肌肉骨骼系统内的异常，在整个发育过程中可能会变得更糟。 这些继发性变化被认为是导致慢性肌肉骨骼疼痛的主要原因。 见于很大比例的 CP 儿童。但目前这方面的知识还严重缺乏 领域，特别是关于持续性疼痛的神经生理学机制，迄今为止的大多数研究 重点关注量化疼痛症状的发生率，而不是潜在的生理学。没有这个 如果没有关键信息，慢性肌肉骨骼疼痛的预防、治疗和评估将不会取得进展。 我们广泛的脑磁图 (MEG) 脑成像程序已发现早期脑损伤 患有 CP 的儿童所经历的体验会导致体感对周围感觉的异常处理 皮质。最近，我们扩展了这些结果，表明患有脑瘫的儿童有更多的异常情况 足部周围刺激后的体感皮质振荡也有较高的疼痛报告。 这种关系意味着体感完整性之间可能存在根本联系。 脑瘫儿童的皮质处理和疼痛感知。该提案的目的是测试我们的 科学前提是，体感神经连接受到干扰，可能是由适应不良引起的 早期脑损伤后的神经塑性变化在患有 CP 的儿童中发生改变，这导致 疼痛感知网络和慢性疼痛的活动增强。我们的方法是“高风险”，但具有 具有显着“回报”的潜力，因为它可能会带来新颖的见解和我们理解的范式转变 CP 儿童的疼痛感知。该提案的具体目标将 (1) 证明 机械感受器和伤害感受器的外周刺激后体感皮层振荡的变化 脚和手会随着孩子感知到的疼痛程度而变化，并且（2）确定体感的强度是否 患有 CP 的儿童中，外周刺激后的皮质振荡存在差异性改变 与高疼痛水平的比较，以及两组是否与典型发育 (TD) 儿童不同。简单来说，我们的研究 将使用 MEG、先进的图像重建方法和时间序列分析来量化 TD 儿童外周机械和伤害感受器刺激后的体感皮层振荡， 以及患有痉挛性双瘫性脑瘫和不同疼痛程度（即严重程度）的儿童。实现我们的目标将提供 对 CP 儿童慢性疼痛的神经基础有深入的了解，并可能引发治疗范式的转变 该人群肌肉骨骼疼痛的主流治疗和评估。